IF7多肽介导隐形纳米粒节拍式化疗逆转肿瘤多药耐药

肿瘤多药耐药（Multi-drug resistance，MDR）是抗肿瘤化疗失败的主要原因。节拍式化疗具有肿瘤抗血管生成活性，有望发展成为逆转肿瘤MDR新策略。本项目首次构建IF7多肽修饰，载具有高活性抗血管生成作用的化疗药物紫杉醇（paclitaxel，PTX），主动靶向肿瘤血管内皮细胞Annexin 1受体的新型隐形纳米粒（IF7-PTX-NP，IPN）。以IPN为主动靶向肿瘤血管模型，进行长期、低剂量、间歇期短的节拍式化疗逆转肿瘤MDR的探索性研究。初步研究结果表明，IPN表现出良好的肿瘤血管内皮细胞靶向特性；显著诱导荷MDR人乳腺癌裸鼠肿瘤血管内皮细胞凋亡和肿瘤组织坏死，提示主动靶向肿瘤血管抗血管生成治疗具有抗肿瘤MDR活性。本项目首次探讨采用节拍式化疗靶向肿瘤血管逆转肿瘤MDR的可行性及其机制；为建立肿瘤MDR治疗新策略和发展节拍式化疗新理论提供理论依据和实验基础。

Multi-drug resistance (MDR) is a major obstacle to the success of cancer chemotherapy. Metronomic chemotherapy aiming at inhibiting tumor angiogenesis with conventional chemotherapeutics is a promising strategy for overcoming MDR. Here, we developed a new nanoparticulate drug delivery system (DDS)- IF7 peptide conjugated, Annexin 1 targeted nanoparticles for paclitaxel (IF7-PTX-NP，IPN), as a model for the investigation of targeted tumor angiogenesis metronomic chemotherapy with respect to reverse MDR. The Preliminary results demonstrate that IPN exerts well tumor angiogenesis targeted and antitumor activity of muti-drug resistence breast cancer.It is mainly through the antiangiogenic effect of PTX, which is specifically delivered into the tumor vascular endothelial cells through the nanoparticle internalization mediated by the interaction of IF7 and over-expressed Annexin 1 receptors on tumor vessels. The present research reveals and highlights the significance of targeted metronomic chemotherapy with nanoparticulate DDS in antiangiogenic cancer therapy. To our knowledge, metronomic chemotherapy is the first time to be used to explore the effect and mechanism of overcoming MDR. Our research provides theory and experimental basis for building new MDR treatment strategy targeted tumor vascular drug delivery systems.